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Background Although current efforts are made to diminish the incidence and burden of disease, cancer is still widely identified late at stage. This study aims to conduct a systematic review mapping the existent and emerging clinical research on artificial intelligence (AI) in the treatment of cancer and to underpin its integration challenges and opportunities in the European Union (EU) health sector. Methods A systematic literature review (SLR) evaluating global clinical trials (CTs; published between 2010 and 2020 or forthcoming) was concluded. Additionally, a horizon scanning (HS) exercise focusing on emerging trends (published between 2017 and 2020) was conducted. Results Forty-four CTs were identified and analyzed. Selected CTs were divided into three research areas: (i) potential of AI combined with imaging techniques, (ii) AI's applicability in robotic surgery interventions and (iii) AI's potential in clinical decision making. Twenty-one studies presented an interventional nature, nine papers were observational and 14 articles did not explicitly mention the type of study performed. The papers presented an increased heterogeneity in sample size, type of tumour, type of study and reporting of results. In addition, a shift in research is observed and only a small fraction of studies were completed in the EU. These findings could be further linked to the current socio-economic, political, scientific, technological and environmental state of the EU in regard to AI innovation. Conclusion To overcome the challenges threatening the EU's integration of such technology in the healthcare field, new strategies taking into account the EU's socio-economic and political environment are deemed necessary. [ABSTRACT FROM AUTHOR]

Background: the worldwide number of dementia cases is increasing, and this is a trend that is expected to continue as a growing proportion of the population ages. However, conducting research with persons suffering from dementia can be fraught due to fears surrounding research risks in vulnerable populations. This can make seeking approval for studies difficult. As research directly involving persons with dementia is key for the development of evidence-based best practice, the development of a coherent ethical strategy to perform such research feasibly and effectively is of paramount importance. Objective: this paper aims to review and synthesise ethical challenges in performing research with persons who have dementia. Methods: in undertaking a systematic review of the current research literature, we will identify the central issues and arguments characterising research that concerns the ethical dimensions of research participation in the dementia population. Data were analysed using both inductive and deductive content analysis. Ethical considerations in research involving persons with dementia primarily concern the representation of the interests of the person with dementia and protection of their vulnerabilities and rights. Results: a total of 2,894 results were returned from initial searches, following deduplication. In total, 2,458 were excluded at title review, and following abstract review 158 papers remained; 29 papers were included for analysis after full paper review and data extraction. Papers ranged between 1995 and 2013. Conclusion: this review has highlighted a lack of consensus in current research and guidelines addressing these concerns; a clear stance on ethical governance of studies is important for future research and best evidence-based practice in dementia. [ABSTRACT FROM AUTHOR]

We examined the importance of understanding and incorporating cultural context within Aotearoa/New Zealand when engaging in clinical research and practice. This paper reports on the qualitative findings of a mixed methods study aimed at determining what effect a cardiac risk reduction exercise and lifestyle management programme, embedded within a kaupapa Māori methodological approach, had on Māori participants. This methodology saw participants able to redevelop a western model cardiac risk reduction programme by introducing a Māori worldview. Our study revealed how the kaupapa Māori approach empowered participants to examine and evaluate not only their own health and lifestyle choices, but those of family and the wider community. Combining biomedical and kaupapa Māori components into the programme was found to benefit participants' mental, physical, spiritual and family well-being. [ABSTRACT FROM AUTHOR]

Online citizen panels are an innovative way to collect information about populations. They can help explain social determinants of health while involving citizens in research, allowing researchers to help the community, and advance cardiovascular research. This paper discusses the advantages and disadvantages of collecting information via online citizen panels and assesses these panels' potential in cardiovascular research. To exemplify such panels' use, we discuss a case study that utilized the Swedish Citizen Panel. [ABSTRACT FROM AUTHOR]

Objectives. To describe existing techniques of US-guided synovial biopsy (USG-SB) and critically appraise the literature on this technology through the OMERACT filter. Methods. USG-SB techniques are described and compared. A systematic literature search of PubMed and Embase was performed for original research reports including US and SB. The subjects, procedure protocols and reported results were analysed. A future research agenda is proposed. Results. USG-SB can be performed using a portal-and-forceps or a dedicated semi-automatic guillotine-type biopsy needle approach. Of 50 reports identified, 7 were included in the review. Large, intermediate and small joints were all amenable to USG-SB. We found great heterogeneity with regard to indications for and definition of a successful procedure and of synovitis. Adverse events were assessed in most papers with an overall major complication rate of 0.4%. However, there was a lack of construct validity using a histological comparator. Relatively few papers reported details on the technique used, tissue processing, synovitis scoring and blinding for tissue analysis. Conclusion. USG-SB can be regarded as a valuable tool for large-scale synovial tissue sampling. Standardization of the techniques of USG-SB and tissue processing is needed. Future research should focus on the reliability, responsiveness and feasibility of this procedure in prospective studies. [ABSTRACT FROM AUTHOR]

The existing literature indicates that motivation is an important predictor of treatment outcome for people with substance use disorders (SUD). Although researchers have found that music therapy can positively impact motivation for people with SUD, the music therapy and SUD literature base lack a theoretical understanding of motivation. Vroom's expectancy theory of motivation (ETM) is an established theoretical framework positing that motivation depends on three relationships: expectancy, instrumentality, and valence. These relationships consist of four variables: effort, performance, reward, and preference. Based on these four variables, motivation depends on the expectation that an increase in effort will lead to improved performance, thus leading to a reward aligned with an individual's preferences. The purpose of this paper is to apply Vroom's ETM to music therapy and SUD clinical practice and research. We reviewed the existing literature addressing Vroom's ETM within SUD treatment and created a model to depict how to apply Vroom's ETM to music therapy clinical practice for people with SUD. Application of Vroom's ETM may help music therapists understand and augment motivation for people with SUD, potentially leading to relapse prevention and recovery. Implications for clinical practice, limitations, and suggestions for future research are provided. [ABSTRACT FROM AUTHOR]

Scotland is a small nation, yet it leads the field in key areas of aging research. With the creation of a devolved government with authority over health and social services, the country has witnessed practice and policy developments that offer distinctive opportunities for innovative research. With multidisciplinary groups of internationally recognized researchers, Scotland is able to take advantage of a unique set of opportunities for aging research: a well-profiled population brings opportunities in population data and linkage to understand people's interactions with health, social care, and other public services; while research on technology and telecare is a distinctive area where Scotland is recognized internationally for using technology to develop effective, high-quality and well-accepted services at relatively low financial cost. The paper also considers free personal care for older people and the national dementia strategy in Scotland. The potential to evaluate the impact of free personal care will provide valuable information for other global health and social care systems. Exploring the impact of the national dementia strategy is another unique area of research that can advance understanding in relation to quality of life and the development of services. The paper concludes that, while Scotland benefits from unique opportunities for progressive public policy and innovative aging research that will provide valuable lessons at the forefront of a globally aging population, the challenges associated with an aging population and increasing cultural diversity must be acknowledged and addressed to ensure that the vision of equality and social justice for all is realized. [ABSTRACT FROM AUTHOR]

Background The Harmonising Outcome Measures for Eczema ( HOME) initiative has defined four core outcome domains for a core outcome set ( COS) to be measured in all atopic eczema ( AE) trials to ensure cross-trial comparison: clinical signs, symptoms, quality of life and long-term control. Objectives The aim of this paper is to report on the consensus process that was used to select the core instrument to consistently assess symptoms in all future AE trials. Methods Following the HOME roadmap, two systematic reviews were performed which identified three instruments that had sufficient evidence of validity, reliability and feasibility to be considered for the final COS. Results At the fourth international HOME meeting, there was broad consensus among all stakeholders that the Patient-Oriented Eczema Measure ( POEM) should be used as the core instrument (87·5% agreed, 9·4% unsure, 3·1% disagreed). Conclusions All relevant stakeholders are encouraged to use POEM as the chosen instrument to measure the core domain of symptoms in all future AE clinical trials. Other instruments of interest can be used in addition to POEM. [ABSTRACT FROM AUTHOR]

Distributed networks of health-care data sources are increasingly being utilized to conduct pharmacoepidemio-logic database studies. Such networks may contain data that are not physically pooled but instead are distributed horizontally (separate patients within each data source) or vertically (separate measures within each data source) in order to preserve patient privacy. While multivariable methods for the analysis of horizontally distributed data are frequently employed, few practical approaches have been put forth to deal with vertically distributed healthcare databases. In this paper, we propose 2 propensity score-based approaches to vertically distributed data analysis and test their performance using 5 example studies. We found that these approaches produced point estimates close to what could be achieved without partitioning. We further found a performance benefit (i.e., lower mean squared error) for sequentially passing a propensity score through each data domain (called the "sequential approach") as compared with fitting separate domain-specific propensity scores (called the "parallel approach"). These results were validated in a small simulation study. This proof-of-concept study suggests a new multivariable analysis approach to vertically distributed health-care databases that is practical, preserves patient privacy, and warrants further investigation for use in clinical research applications that rely on health-care databases. [ABSTRACT FROM AUTHOR]

For the analysis of longitudinal or repeated measures data, generalized linear mixed-effects models provide a flexible and powerful tool to deal with heterogeneity among subject response profiles. However, the typical statistical design adopted in usual randomized controlled trials is an analysis of covariance type analysis using a pre-defined pair of "pre-post" data, in which pre-(baseline) data are used as a covariate for adjustment together with other covariates. Then, the major design issue is to calculate the sample size or the number of subjects allocated to each treatment group. In this paper, we propose a new repeated measures design and sample size calculations combined with generalized linear mixed-effects models that depend not only on the number of subjects but on the number of repeated measures before and after randomization per subject used for the analysis. The main advantages of the proposed design combined with the generalized linear mixed-effects models are (1) it can easily handle missing data by applying the likelihood-based ignorable analyses under the missing at random assumption and (2) it may lead to a reduction in sample size, compared with the simple pre-post design. The proposed designs and the sample size calculations are illustrated with real data arising from randomized controlled trials. [ABSTRACT FROM AUTHOR]

The article reports disparity and social unrest amid COVID-19 pandemic. It mentions Black, Latinx, and other non-White individuals account for 60 per cent of COVID-19 deaths; and also mentions genetic or physiologic reason that COVID-19 is a more serious infection among Black or Latinx people than White people, then race or ethnicity should be an independent predictor of mortality.

Background. In this paper, we provide background and context regarding the potential for a new data-sharing platform, the Project Data Sphere (PDS) initiative, funded by financial and in-kind contributions from the CEO Roundtable on Cancer, to transform cancer research and improve patient outcomes. Given the relatively modest decline in cancer death rates over the past several years, a new research paradigm is needed to accelerate therapeutic approaches for oncologic diseases. Phase III clinical trials generate large volumes of potentially usable information, often on hundreds of patients, including patients treated with standard of care therapies (i.e., controls). Both nationally and internationally, a variety of stakeholders have pursued data-sharing efforts to make individual patient-level clinical trial data available to the scientific research community. Potential Benefits and Risks of Data Sharing. For researchers, shared data have the potential to foster amore collaborative environment, to answer research questions in a shorter time frame than traditional randomized control trials, to reduce duplication of effort, and to improve efficiency. For industry participants, use of trial data to answer additional clinical questions could increase research and development efficiency and guide future projects through validation of surrogate end points, development of prognostic or predictive models, selection of patients for phase II trials, stratification in phase III studies, and identification of patient subgroups for development of novel therapies. Data transparency also helps promote a public image of collaboration and altruism among industry participants. For patient participants, data sharing maximizes their contribution to public health and increases access to information that may be used to develop better treatments. Concerns about data-sharing efforts include protection of patient privacy and confidentiality. To alleviate these concerns, data sets are deidentified to maintain anonymity. To address industry concerns about protection of intellectual property and competitiveness, we illustrate several models for data sharing with varying levels of access to the data and varying relationships between trial sponsors and data access sponsors. The Project Data Sphere Initiative. PDS is an independent initiative of the CEO Roundtable on Cancer Life Sciences Consortium, built to voluntarily share, integrate, and analyze comparator arms of historical cancer clinical trial data sets to advance future cancer research. The aim is to provide a neutral, broad-access platform for industry and academia to share raw, deidentified data from late-phase oncology clinical trials using comparator-arm data sets. These data are likely to be hypothesis generating or hypothesis confirming but, notably, do not take the place of performing a well-designed trial to address a specific hypothesis. Prospective providers of data to PDS complete and sign a data sharing agreement that includes a description of the data they propose to upload, and then they follow easy instructions on the website for uploading their deidentified data. The SAS Institute has also collaborated with the initiative to provide intrinsic analytic tools accessible within the website itself. As of October 2014, the PDS website has available data from 14 cancer clinical trials covering 9,000 subjects, with hopes to further expand the database to include more than 25,000 subject accruals within the next year. PDS differentiates itself from other data-sharing initiatives by its degree of openness, requiring submission of only a brief application with background information of the individual requesting access and agreement to terms of use. Data from several different sponsors may be pooled to develop a comprehensive cohort for analysis. In order to protect patient privacy, data providers in the U.S. are responsible for deidentifying data according to standards set forth by the Privacy Rule of the U.S. Health Insurance Portability and Accountability Act of 1996. Using Data Sharing to Improve Outcomes in Cancer: The "Prostate Cancer Challenge." Control-arm data of several studies among patients with metastatic castration-resistant prostate cancer (mCRPC) are currently available through PDS. These data sets have multiple potential uses. The "Prostate Cancer Challenge" will ask the cancer research community to use clinical trial data deposited in the PDS website to address key research questions regarding mCRPC. General themes that could be explored by the cancer community are described in this article: prognostic models evaluating the influence of pretreatment factors on survival and patient-reported outcomes; comparative effectiveness research evaluating the efficacy of standard of care therapies, as illustrated in our companion article comparing mitoxantrone plus prednisone with prednisone alone; effects of practice variation in dose, frequency, and duration of therapy; level of patient adherence to elements of trial protocols to inform the design of future clinical trials; and age of subjects, regional differences in health care, and other confounding factors that might affect outcomes. Potential Limitations and Methodological Challenges. The number of data sets available and the lack of experiment alarm data limit the potential scope of research using the current PDS. The number of trials is expected to grow exponentially over the next year and may include multiple cancer settings, such as breast, colorectal, lung, hematologic malignancy, and bone marrow transplantation. Other potential limitations include the retrospective nature of the data analyses performed using PDS and its generalizability, given that clinical trials are often conducted among younger, healthier, and less racially diverse patient populations. Methodological challenges exist when combining individual patient data from multiple clinical trials; however, advancements in statistical methods for secondary database analysis offer many tools for reanalyzing data arising from disparate trials, such as propensity score matching. Despite these concerns, few if any comparable data sets include this level of detail across multiple clinical trials and populations. Conclusion. Access to large, late-phase, cancer-trial data sets has the potential to transform cancer research by optimizing research efficiency and accelerating progress toward meaningful improvements in cancer care. This type of platform provides opportunities for unique research projects that can examine relatively neglected areas and that can construct models necessitating large amounts of detailed data.The full potential of PDS will be realized only when multiple tumor types and larger numbers of data sets are available through the website. [ABSTRACT FROM AUTHOR]

In May 2019, the US Food and Drug Administration (FDA) released the Framework for FDA's Real-World Evidence (RWE) Program, a draft guidance to evaluate the potential use of real-world data in facilitating regulatory decisions. As a result, pharmaceutical companies and medical communities see patient registries, which are large, prospective, noninterventional cohort studies, as becoming increasingly important in providing evidence of treatment effectiveness and safety in clinical practice. Patient registries are designed to collect longitudinal clinical data on a broad population to address critical medical questions over time. With their large sample sizes and broad inclusion criteria, patient registries are often used to generate RWE in the general and underrepresented patient populations that are less likely to be studied in controlled clinical trials. Here, we describe the value of industry-sponsored patient registries in oncology/hematology settings to healthcare stakeholders, in drug development, and in fostering scientific collaboration. [ABSTRACT FROM AUTHOR]

Background African countries are underrepresented in cancer research, partly because of a lack of structured curricula on clinical research during medical education. To address this need, the MD Anderson and Zambia Virtual Clinical Research Training Program (MOZART) was developed jointly by MD Anderson Cancer Center (MDA) and the Cancer Diseases Hospital in Zambia (CDH) for Zambian clinical oncology trainees. We explored participant perspectives to provide insight for implementation of similar efforts. Materials and Methods The MD Anderson and Zambia Virtual Clinical Research Training Program consisted of weekly virtual lectures and support of Zambian-led research protocols through longitudinal mentorship groups that included CDH faculty and MDA peer and faculty mentors. Participants were contacted via email to take part in semi-structured interviews, which were conducted via teleconference and audio-recorded, transcribed, and coded. Emergent themes were extracted and are presented with representative verbatim quotations. Results Thirteen of the 14 (93%) trainees were interviewed. Emergent themes included (1) participants having diverse educational backgrounds but limited exposure to clinical research, (2) importance of cancer research specific to a resource-constrained setting, (3) complementary roles of peer mentors and local and international faculty mentors, (4) positive impact on clinical research skills but importance of a longitudinal program and early exposure to clinical research, and (5) challenges with executing research protocols. Conclusion To our knowledge, this is the first qualitative study of African clinical oncology trainees participating in a virtual clinical research training program. The lessons learned from semi-structured interviews with participants in MOZART provided valuable insights that can inform the development of similar clinical research training efforts and scale-up. [ABSTRACT FROM AUTHOR]

Introduction Communication breakdown is a factor in the majority of all instances of medical error. Despite the importance, a relative paucity of time is invested in communication skills in postgraduate curricula. Our objective is to systematically review the literature to identify the current tools used to assess communication skills in postgraduate trainees in the latter 2 years of training and in established practice. Methods Two reviewers independently reviewed the literature identifying communication skill assessment tools, for postgraduate trainees in the latter 2 years of training and in established practice following Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework, and inclusion/exclusion criteria from January 1990 to 15 August 2014. Databases: PubMed/ CINAHL/ERIC/EMBASE/PsycInfo/Psyc Articles/Cochrane. Results 222 articles were identified; after review, 34 articles fulfilled criteria for complete evaluation; the majority (26) had a high level of evidence scoring 3 or greater on the Best Evidence Medical Education guide. 22 articles used objective structured clinical examination/ standardised patient (SP)-based formats in an assessment or training capacity. Evaluation tools included author-developed questionnaires and validated tools. Nineteen articles demonstrated an educational initiative. Conclusions The reviewed literature is heterogeneous for objectives and measurement techniques for communication. Observed interactions, with patients or SPs, is the current favoured method of evaluation using author-developed questionnaires. The role of self-evaluation of skill level is questioned. The need for a validated assessment tool for communication skills is highlighted. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses articles in the issue on topics including treatments/exposure groups are weighted to help minimize bias in comparisons, and the random intercepts cross-lagged panel model is discussed as a method of causal inference.

The COVID-19 pandemic resulted in catastrophic levels of morbidity and mortality for care home residents. Despite this, research platforms for COVID-19 in care homes arrived late in the pandemic compared with other care settings. The Prophylactic Therapy in Care Homes Trial (PROTECT-CH) was established to provide a platform to deliver multi-centre cluster-randomized clinical trials of investigational medicinal products for COVID-19 prophylaxis in UK care homes. Commencing set-up in January 2021, this involved the design and development of novel infrastructure for contracting and recruitment, remote consent, staff training, research insurance, eligibility screening, prescribing, dispensing and adverse event reporting; such infrastructure being previously absent. By the time this infrastructure was in place, the widespread uptake of vaccination in care homes had changed the epidemiology of COVID-19 rendering the trial unfeasible. While some of the resources developed through PROTECT-CH will enable the future establishment of care home platform research, the near absence of care home trial infrastructure and nationally linked databases involving the care home sector will continue to significantly hamper progress. These issues are replicated in most other countries. Beyond COVID-19, there are many other research questions that require addressing to provide better care to people living in care homes. PROTECT-CH has exposed a clear need for research funders to invest in, and legislate for, an effective care home research infrastructure as part of national pandemic preparedness planning. Doing so would also invigorate care home research in the interim, leading to improved healthcare delivery specific to those living in this sector. [ABSTRACT FROM AUTHOR]

A correction to the article "Health Research and Knowledge Translation for Achieving the Sustainable Development Goals: Tackling the Hurdles" that was published in the March 23, 2020 issue is presented.

In this article, music therapy researchers and clinicians share lessons learned through engaging in collaborative research with healthcare providers in community settings. Practical aspects of conducting research in community health settings are discussed, including consulting on-site music therapists, healthcare providers, and administrators in the earliest stages of research planning; integration of research team members with community healthcare providers; and strategies for successful study implementation. We present our experiences of challenges surrounding the aspects of study implementation, such as recruitment, obtaining consent, and collecting outcome data, as well as opportunities that have resulted from our work, such as increased visibility for music therapy services, collaboration on protocol refinement, and continuing music therapy services beyond the study. Throughout the article, we refer to two research studies that illustrate the collaborative process as well as offer practical examples of challenges and problem-solving. [ABSTRACT FROM AUTHOR]

Aim The purpose of this brief narrative review is to address the complexities and benefits of extending animal alcohol addiction research to the human domain, emphasizing Allostasis and Incentive Sensitization, two models that inform many pre-clinical and clinical studies. Methods The work reviewed includes a range of approaches, including: a) animal and human studies that target the biology of craving and compulsive consumption; b) human investigations that utilize alcohol self-administration and alcohol challenge paradigms, in some cases across 10 years; c) questionnaires that document changes in the positive and negative reinforcing effects of alcohol with increasing severity of addiction; and d) genomic structural equation modeling based on data from animal and human studies. Results Several general themes emerge from specific study findings. First, positive reinforcement is characteristic of early stage addiction and sometimes diminishes with increasing severity, consistent with both Allostasis and Incentive Sensitization. Second, evidence is less consistent for the predominance of negative reinforcement in later stages of addiction, a key tenant of Allostasis. Finally, there are important individual differences in motivation to drink at a given point in time as well as person-specific change patterns across time. Conclusions Key constructs of addiction, like stage and reinforcement, are by necessity operationalized differently in animal and human studies. Similarly, testing the validity of addiction models requires different strategies by the two research domains. Although such differences are challenging, they are not insurmountable, and there is much to be gained in understanding and treating addiction by combining pre-clinical and clinical approaches. [ABSTRACT FROM AUTHOR]

Shortcomings in the current pipeline of infectious disease physician scientists are well documented. With a focus on the transition of early stage investigators to research independence, we outline challenges in existing training pathways for physician scientists. We urge leaders of infectious disease societies, divisions, and governmental and nongovernmental funding organizations to reinvigorate a vision for nurturing trainees with interests in research, to seek transparency in physician scientist funding mechanisms, and to encourage efforts to improve the reproducibility of outcomes for talented junior investigators. We feel that the alternative to making these changes will lead to further drop-off in the physician scientist pipeline in a field that has a perpetual need for research. [ABSTRACT FROM AUTHOR]

The Department of Epidemiology at Johns Hopkins School of Hygiene and Public Health was founded in 1919, with Wade Hampton Frost as inaugural chair. In our Centennial Year, we review how our research and educational programs have changed. Early years focused on doctoral education in epidemiology and some limited undergraduate training for practice. Foundational work on concepts and methods linked to the infectious diseases of the day made major contributions to study designs and analytical methodologies, largely still in use. With the epidemiologic transition from infectious to chronic disease, new methods were developed. The Department of Chronic Diseases merged with the Department of Epidemiology in 1970, under the leadership of Abraham Lilienfeld. Leon Gordis became chair in 1975, and multiple educational tracks were developed. Genetic epidemiology began in 1979, followed by advances in infectious disease epidemiology spurred by the human immunodeficiency virus/acquired immune deficiency syndrome epidemic. Collaborations with the Department of Medicine led to development of the Welch Center for Prevention, Epidemiology, and Clinical Research in 1989. Between 1994 and 2008, the department experienced rapid growth in faculty and students. A new methods curriculum was instituted for upper-level epidemiologic training in 2006. Today's research projects are increasingly collaborative, taking advantage of new technologies and methods of data collection, responding to "big data" analysis challenges. In our second century, the department continues to address issues of disease etiology and epidemiologic practice. [ABSTRACT FROM AUTHOR]

Background routine frailty identification and management is national policy in England, but there remains a lack of evidence on the impact of frailty on healthcare resource use. We evaluated the impact of frailty on the use and costs of general practice and hospital care. Methods retrospective longitudinal analysis using linked routine primary care records for 95,863 patients aged 65–95 years registered with 125 UK general practices between 2003 and 2014. Baseline frailty was measured using the electronic Frailty Index (eFI) and classified in four categories (non, mild, moderate, severe). Negative binomial regressions and ordinary least squares regressions with multilevel mixed effects were applied on the use and costs of general practice and hospital care. Results compared with non-frail status, annual general practitioner consultation incidence rate ratios (IRRs) were 1.24 (95% CI: 1.21–1.27) for mild, 1.41 (95% CI: 1.35–1.47) for moderate, and 1.52 (95% CI: 1.42–1.62) for severe frailty. For emergency hospital admissions, the respective IRRs were 1.64 (95% CI 1.60–1.68), 2.45 (95% CI 2.37–2.53) and 3.16 (95% CI: 3.00–3.33). Compared with non-frail people the IRR for inpatient days was 7.26 (95% CI 6.61–7.97) for severe frailty. Using 2013/14 reference costs, extra annual cost to the healthcare system per person was £561.05 for mild, £1,208.60 for moderate and £2,108.20 for severe frailty. This equates to a total additional cost of £5.8 billion per year across the UK. Conclusions increasing frailty is associated with substantial increases in healthcare costs, driven by increased hospital admissions, longer inpatient stay, and increased general practice consultations. [ABSTRACT FROM AUTHOR]

Authors aiming to estimate causal effects from observational data frequently discuss 3 fundamental identifiability assumptions for causal inference: exchangeability, consistency, and positivity. However, too often, studies fail to acknowledge the importance of measurement bias in causal inference. In the presence of measurement bias, the aforementioned identifiability conditions are not sufficient to estimate a causal effect. The most fundamental requirement for estimating a causal effect is knowing who is truly exposed and unexposed. In this issue of the Journal , Caniglia et al. (Am J Epidemiol. 2019;000(00):000–000) present a thorough discussion of methodological challenges when estimating causal effects in the context of research on distance to obstetrical care. Their article highlights empirical strategies for examining nonexchangeability due to unmeasured confounding and selection bias and potential violations of the consistency assumption. In addition to the important considerations outlined by Caniglia et al. authors interested in estimating causal effects from observational data should also consider implementing quantitative strategies to examine the impact of misclassification. The objective of this commentary is to emphasize that you can't drive a car with only three wheels, and you also cannot estimate a causal effect in the presence of exposure misclassification bias. [ABSTRACT FROM AUTHOR]

Background: Infectious disease interventions are increasingly tested using cluster-randomized trials (CRTs). These trial settings tend to involve a set of sampling units, such as villages, whose geographic arrangement may present a contamination risk in treatment exposure. The most widely used approach for reducing contamination in these settings is the so-called fried-egg design, which excludes the outer portion of all available clusters from the primary trial analysis. However, the fried-egg design ignores potential intra-cluster spatial heterogeneity and makes the outcome measure inherently less precise. Whereas the fried-egg design may be appropriate in specific settings, alternative methods to optimize the design of CRTs in other settings are lacking.Methods: We present a novel approach for CRT design that either fully includes or fully excludes available clusters in a defined study region, recognizing the potential for intra-cluster spatial heterogeneity. The approach includes an algorithm that allows investigators to identify the maximum number of clusters that could be included for a defined study region and maintain randomness in both the selection of included clusters and the allocation of clusters to either the treatment group or control group. The approach was applied to the design of a CRT testing the effectiveness of malaria vector-control interventions in southern Malawi.Conclusions: Those planning CRTs to evaluate interventions should consider the approach presented here during trial design. The approach provides a novel framework for reducing the risk of contamination among the CRT randomization units in settings where investigators determine the reduction of contamination risk as a high priority and where intra-cluster spatial heterogeneity is likely. By maintaining randomness in the allocation of clusters to either the treatment group or control group, the approach also permits a randomization-valid test of the primary trial hypothesis. [ABSTRACT FROM AUTHOR]

The risk difference scale is often of primary interest when evaluating public health impacts of interventions on binary outcomes. However, few investigators report findings in terms of additive interaction, probably because the models typically used for binary outcomes implicitly measure interaction on the multiplicative scale. One measure with which to assess additive interaction from multiplicative models is the relative excess risk due to interaction (RERI). The RERI measure has been applied in many contexts, but one limitation of previous approaches is that clustering in data has rarely been considered. We evaluated the RERI metric for the setting of clustered data using both population-averaged and cluster-conditional models. In simulation studies, we found that estimation and inference for the RERI using population-averaged models was straightforward. However, frequentist implementations of cluster-conditional models including random intercepts often failed to converge or produced degenerate variance estimates. We developed a Bayesian implementation of log binomial random-intercept models, which represents an attractive alternative for estimating the RERI in cluster-conditional models. We applied the methods to an observational study of adverse birth outcomes in mothers with human immunodeficiency virus, in which mothers were clustered within clinical research sites. [ABSTRACT FROM AUTHOR]

Background: This was an 8-year follow-up of an RCT comparing ultrasound-guided foam sclerotherapy (UGFS) with high ligation and surgical stripping (HL/S) of the great saphenous vein (GSV). Methods: Patients were randomized to UGFS or HL/S of the GSV. The primary outcome was the recurrence of symptomatic GSV reflux. Secondary outcomes were patterns of reflux according to recurrent varices after surgery, Clinical Etiologic Anatomic Pathophysiologic (CEAP) classification, Venous Clinical Severity Score (VCSS) and EuroQol Five Dimensions (EQ-5D™) quality-of-life scores. Results: Of 430 patients originally randomized (230 UGFS, 200 HL/S), 227 (52.8 per cent; 123 UGFS, 103 HL/S) were available for analysis after 8 years. The proportion of patients free from symptomatic GSV reflux at 8 years was lower after UGFS than HL/S (55.1 versus 72.1 per cent; P = 0.024). The rate of absence of GSV reflux, irrespective of venous symptoms, at 8 years was 33.1 and 49.7 per cent respectively (P = 0.009). More saphenofemoral junction (SFJ) failure (65.8 versus 41.7 per cent; P = 0.001) and recurrent reflux in the above-knee GSV (72.5 versus 20.4 per cent; P = 0.001) was evident in the UGFS group. The VCSS was worse than preoperative scores in both groups after 8 years; CEAP classification and EQ-5D® scores were similar in the two groups. Conclusion: Surgical stripping had a technically better outcome in terms of recurrence of GSV and SFJ reflux than UGFS in the long term. Long-term follow-up suggests significant clinical progression of venous disease measured by VCSS in both groups, but less after surgery. [ABSTRACT FROM AUTHOR]

Summary: Background: Scratching and itch are common clinical signs of atopic dermatitis (AD). Studies of adult patients have shown that a decrease in scratching behaviour results in regression of inflammation and improved healing of the skin. Objectives: To investigate whether a modified habit reversal (HR) treatment protocol could be used for the treatment of scratching in children to improve skin status. Methods: The study is a single‐blind, randomized controlled trial of 39 patients who started with registration a week before randomization into one of two groups (intervention or control). The participants in the intervention group received a habit‐breaking therapy of their scratching behaviour (i.e. HR) in addition to a potent steroid (mometasone furoate), whereas the patients in the control group received the steroid alone. The patients were assessed by an independent dermatologist after the first week of registration (baseline assessment) and then after 3 and 8 weeks of treatment. The primary efficacy variable was a change in objective Scoring Atopic Dermatitis (SCORAD). Results: At the end of the 3‐week treatment period, the change in mean objective SCORAD was significantly (P = 0·027) higher in the intervention group (−31·9 ± 9·5) than in the control group (−23·8 ± 10·1). After the 8‐week follow‐up, the change in mean objective SCORAD was significantly (P = 0·0038) higher in the intervention group (−31·7 ± 10·4) than in the control group (−19·7 ± 9·4). Conclusions: The treatment of scratching with the HR method in combination with a potent steroid was found to improve skin status significantly after 3 and 11 weeks. [ABSTRACT FROM AUTHOR]

Objective: Quality improvement of health care requires robust measurable indicators to track performance. However identifying which indicators are supported by strong clinical evidence, typically from clinical trials, is often laborious. This study tests a novel method for automatically linking indicators to clinical trial registrations.Design: A set of 522 quality of care indicators for 22 common conditions drawn from the CareTrack study were automatically mapped to outcome measures reported in 13 971 trials from ClinicalTrials.gov.Intervention: Text mining methods extracted phrases mentioning indicators and outcome phrases, and these were compared using the Levenshtein edit distance ratio to measure similarity.Main Outcome Measure: Number of care indicators that mapped to outcome measures in clinical trials.Results: While only 13% of the 522 CareTrack indicators were thought to have Level I or II evidence behind them, 353 (68%) could be directly linked to randomized controlled trials. Within these 522, 50 of 70 (71%) Level I and II evidence-based indicators, and 268 of 370 (72%) Level V (consensus-based) indicators could be linked to evidence. Of the indicators known to have evidence behind them, only 5.7% (4 of 70) were mentioned in the trial reports but were missed by our method.Conclusions: We automatically linked indicators to clinical trial registrations with high precision. Whilst the majority of quality indicators studied could be directly linked to research evidence, a small portion could not and these require closer scrutiny. It is feasible to support the process of indicator development using automated methods to identify research evidence. [ABSTRACT FROM AUTHOR]

Background Laparoscopic left lateral sectionectomy ( LLLS) has been associated with shorter hospital stay and reduced overall morbidity compared with open left lateral sectionectomy ( OLLS). Strong evidence has not, however, been provided. Methods In this multicentre double-blind RCT, patients (aged 18-80 years with a BMI of 18-35 kg/m2 and ASA fitness grade of III or below) requiring left lateral sectionectomy ( LLS) were assigned randomly to OLLS or LLLS within an enhanced recovery after surgery ( ERAS) programme. All randomized patients, ward physicians and nurses were blinded to the procedure undertaken. A parallel prospective registry (open non-randomized ( ONR) versus laparoscopic non-randomized ( LNR)) was used to monitor patients who were not enrolled for randomization because of doctor or patient preference. The primary endpoint was time to functional recovery. Secondary endpoints were length of hospital stay ( LOS), readmission rate, overall morbidity, composite endpoint of liver surgery-specific morbidity, mortality, and reasons for delay in discharge after functional recovery. Results Between January 2010 and July 2014, patients were recruited at ten centres. Of these, 24 patients were randomized at eight centres, and 67 patients from eight centres were included in the prospective registry. Owing to slow accrual, the trial was stopped on the advice of an independent Data and Safety Monitoring Board in the Netherlands. No significant difference in median (i.q.r.) time to functional recovery was observed between laparoscopic and open surgery in the randomized or non-randomized groups: 3 (3-5) days for OLLS versus 3 (3-3) days for LLLS; and 3 (3-3) days for ONR versus 3 (3-4) days for LNR. There were no significant differences with regard to LOS, morbidity, reoperation, readmission and mortality rates. Conclusion This RCT comparing open and laparoscopic LLS in an ERAS setting was not able to reach a conclusion on time to functional recovery, because it was stopped prematurely owing to slow accrual. Registration number: NCT00874224 ( ). [ABSTRACT FROM AUTHOR]

Objectives: After a long history of neglect, diversity among older people and increasing heterogeneity with age are now familiar ideas in gerontological discourse. We take up the question of whether this increased attention is translating into the domain of empirical research. We replicate Nelson and Dannefer's (1992) review of the treatment of age-based variability in gerontological research, the most recent known assessment of the issue. Method: A sample of empirical studies was drawn from six gerontological journals to determine (a) whether measures of within-age variability were reported and/or discussed and (b) if reported, the observed age-based pattern of variability in the outcome(s). Results: The majority of studies neither reported nor discussed age-based variability. Among those that did report, the great majority indicated either stability or increasing variability with age. Observed patterns varied by outcome type. Although a majority of analyses of psychological and social outcomes suggested that variability was stable across age, half of the analyses of biological/health outcomes indicated increasing variability. Overall, very few (3%) of studies suggested decreasing variability. Discussion: Consistent with earlier reports of studies, researchers continue to focus on average differences between age groups, yet key issues in social gerontology require attention to intra-age variability. [ABSTRACT FROM AUTHOR]

Background The complexity of surgical interventions has major implications for the design of RCTs. Trials need to consider how and whether to standardize interventions so that, if successful, they can be implemented in practice. Although guidance exists for standardizing non-pharmaceutical interventions in RCTs, their application to surgery is unclear. This study reports new methods for standardizing the delivery of surgical interventions in RCTs. Methods Descriptions of 160 surgical interventions in existing trial reports and protocols were identified. Initially, ten reports were scrutinized in detail using a modified framework approach for the analysis of qualitative data, which informed the development of a preliminary typology. The typology was amended with iterative sequential application to all interventions. Further testing was undertaken within ongoing multicentre RCTs. Results The typology has three parts. Initially, the overall technical purpose of the intervention is described (exploration, resection and/or reconstruction) in order to establish its constituent components and steps. This detailed description of the intervention is then used to establish whether and how each component and step should be standardized, and the standards documented within the trial protocol. Finally, the typology provides a framework for monitoring the agreed intervention standards during the RCT. Pilot testing within ongoing RCTs enabled standardization of the interventions to be agreed, and case report forms developed to capture deviations from these standards. Conclusion The typology provides a framework for use during trial design to standardize the delivery of surgical interventions and document these details within protocols. Application of this typology to future RCTs may clarify details of the interventions under evaluation and help successful interventions to be implemented. [ABSTRACT FROM AUTHOR]

Although the measurements of clinical outcomes for cancer treatments have become diverse and complex, there remains a need for clear, easily interpreted representations of patients' experiences. With oncology trials increasingly reporting non-time-to-event outcomes, data visualization has evolved to incorporate parameters such as responses to therapy, duration and degree of response, and novel representations of underlying tumor biology. We review both commonly used and newly developed methods to display outcomes in oncology, with a focus on those that have evolved to represent complex datasets. [ABSTRACT FROM AUTHOR]

Objective: To study the efficiency of research implementation in a large radiotherapy institute, in either an internal review board-approved clinical trial or clinical routine. Methods: Scientific publications of the institute were listed. We asked clinicians from tumour expert groups whether the study had been implemented yet in a clinical trial or in clinical practice and which facilitators or barriers were relevant. An independent investigator verified all results. We calculated the implementation rates and the frequency of mentioned facilitators and barriers. Results: Resident researchers had published 234 studies over the past 4 years. Overall, 70/234 (30%) technical or preclinical studies were tested or implemented in a clinical environment in either trials or routine. In total, 45/234 (19%) studies were routinely implemented; in the 61 clinical studies, this percentage was higher: 38% (23/61). The main facilitator was the level of evidence and the main barriers were workload and high complexity. Conclusion: We were able to calculate the implementation ratio of published research into clinical practice and set benchmark figures for other radiotherapy clinics. Level of evidence was an important facilitator, while workload and high complexity of the new procedures were important barriers for implementation. Recent articles suggest that academic entrepreneurship will facilitate this process further. [ABSTRACT FROM AUTHOR]

People can conceptualize the same action (e.g. 'riding a bike') at different levels of abstraction (LOA), where higher LOAs specify the abstract motives that explain why the action is performed (e.g. 'getting exercise'), while lower LOAs specify the concrete steps that indicate how the action is performed (e.g. 'gripping handlebars'). Prior neuroimaging studies have shown that why and how questions about actions differentially activate two cortical networks associated with mental-state reasoning and action representation, respectively; however, it remains unknown whether this is due to the differential demands of the questions per se or to the shifts in LOA those questions produce. We conducted functional magnetic resonance imaging while participants judged pairs of action phrases that varied in LOA and that could be framed either as a why question (Why ride a bike? Get exercise.) or a how question (How to get exercise? Ride a bike.). Question framing (why vs how) had no effect on activity in regions of the two networks. Instead, these regions uniquely tracked parametric variation in LOA, both across and within trials. This suggests that the human capacity to understand actions at different LOA is based in the relative activity of two cortical networks. [ABSTRACT FROM AUTHOR]

We propose a Bayesian phase I/II dose-finding trial design that simultaneously accounts for toxicity and efficacy. We model the toxicity and efficacy of investigational doses using a flexible Bayesian dynamic model, which borrows information across doses without imposing stringent parametric assumptions on the shape of the dose-toxicity and dose-efficacy curves. An intuitive utility function that reflects the desirability trade-offs between efficacy and toxicity is used to guide the dose assignment and selection. We also discuss the extension of this design to handle delayed toxicity and efficacy. We conduct extensive simulation studies to examine the operating characteristics of the proposed method under various practical scenarios. The results show that the proposed design possesses good operating characteristics and is robust to the shape of the dose-toxicity and dose-efficacy curves. [ABSTRACT FROM AUTHOR]

We provide an asymptotic test to analyze randomized clinical trials that may be subject to selection bias. For normally distributed responses, and under permuted block randomization, we derive a likelihood ratio test of the treatment effect under a selection bias model. A likelihood ratio test of the presence of selection bias arises from the same formulation. We prove that the test is asymptotically chi-square on one degree of freedom. These results correlate well with the likelihood ratio test of Ivanova et al. (2005, Statistics in Medicine 24, 1537-1546) for binary responses, for which they established by simulation that the asymptotic distribution is chi-square. Simulations also show that the test is robust to departures from normality and under another randomization procedure. We illustrate the test by reanalyzing a clinical trial on retinal detachment. [ABSTRACT FROM AUTHOR]

Achieving rapid and meaningful improvement in healthcare requires the dissemination of quality improvement project results via publication. Doing this well requires detailed descriptions of the complex interventions and of the context in which the improvement took place. This report builds on the first 2 articles in the series to cover important considerations in writing quality improvement manuscripts with a focus on how it differs from writing traditional clinical research reports. The recommendations we outline here also apply to reviewing quality improvement manuscripts. [ABSTRACT FROM AUTHOR]

The article presents a response from the authors regarding the study "Recommended Patient-Reported Core Set of Symptoms to Measure in Adult Cancer Treatment Trials." Topics discussed include cancer trials for a clear rationale for core outcome sets (COS); the justification for developing and using COS in oncology; and the rationale and approach promoted by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative.

Background Consensus indicates that a comprehensive, multimodal, holistic approach is foundational to the practice of acute pain medicine (APM), but lack of uniform, evidence-based clinical pathways leads to undesirable variability throughout U. S. healthcare systems. Acute pain studies are inconsistently synthesized to guide educational programs. Advanced practice techniques involving regional anesthesia assume the presence of a physician-led, multidisciplinary acute pain service, which is often unavailable or inconsistently applied. This heterogeneity of educational and organizational standards may result in unnecessary patient pain and escalation of healthcare costs. Methods A multidisciplinary panel was nominated through the APM Shared Interest Group of the American Academy of Pain Medicine. The panel met in Chicago, IL, in July 2014, to identify gaps and set priorities in APM research and education. Results The panel identified three areas of critical need: 1) an open-source acute pain data registry and clinical support tool to inform clinical decision making and resource allocation and to enhance research efforts; 2) a strong professional APM identity as an accredited subspecialty; and 3) educational goals targeted toward third-party payers, hospital administrators, and other key stakeholders to convey the importance of APM. Conclusion This report is the first step in a 3-year initiative aimed at creating conditions and incentives for the optimal provision of APM services to facilitate and enhance the quality of patient recovery after surgery, illness, or trauma. The ultimate goal is to reduce the conversion of acute pain to the debilitating disease of chronic pain. [ABSTRACT FROM AUTHOR]

Background: Prior cancer is a common exclusion criterion in lung cancer trials. This practice reflects concerns that prior cancer may affect trial conduct or outcomes. However, the impact of prior cancer on survival in lung cancer is not known. Methods: We identified patients older than age 65 years with stage IV lung cancer diagnosed between 1992 and 2009 in the Surveillance, Epidemiology, and End Results-Medicare linked registry. Prior cancer was characterized by type, stage, and timing. All-cause and lung cancer-specific survival were compared between patients with and without prior cancer using propensity score-adjusted Cox regression. Results: Overall, 102 929 patients with stage IV lung cancer were identified, of whom 14.7% had a history of prior cancer. More than two-thirds (76.0%) of prior cancers were localized or regional stage; most were diagnosed five or fewer years prior to the lung cancer diagnosis. In propensity score-adjusted analysis, patients with prior cancer had better all-cause (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.91 to 0.94) and lung cancer-specific (HR = 0.81, 95% CI = 0.79 to 0.82) survival. In a simulated clinical trial-eligible population (age <75 years, no comorbidity, treated with chemotherapy), similar trends were noted. In subset analyses according to stage, type, and timing of prior cancer, no group of patients with prior cancer had inferior survival compared with patients without prior cancer. Conclusion: Among patients with stage IV lung cancer, prior cancer does not convey an adverse effect on clinical outcomes, regardless of prior cancer stage, type, or timing. Broader inclusion in clinical trials of advanced lung cancer patients with a history of prior cancer should be considered. [ABSTRACT FROM AUTHOR]

Background: Phase I trials often include a dose expansion cohort (DEC), in which additional patients are treated at the estimated maximum tolerated dose (MTD) after dose escalation, with the goal of ensuring that data are available from more than six patients at a single dose level. However, protocols do not always detail how, or even if, the additional toxicity data will be used to reanalyze the MTD or whether observed toxicity in the DEC will warrant changing the assigned dose. A DEC strategy has not been statistically justified. Methods: We conducted a simulation study of two phase I designs: the "3+3" and the Continual Reassessment Method (CRM). We quantified how many patients are assigned the true MTD using a 10 to 20 patient DEC and how a sensible reanalysis using the DEC changes the probability of selecting the true MTD. We compared these results with those from an equivalently sized larger CRM that does not include a DEC. Results: With either the 3+3 or CRM, reanalysis with the DEC increased the probability of identifying the true MTD. However, a large CRM without a DEC was more likely to identify the true MTD while still treating 10 or 15 patients at this dose level. Conclusions: Where feasible, a CRM design with no explicit DEC is preferred to designs that fix a dose for all patients in a DEC. [ABSTRACT FROM AUTHOR]

Mucinous lesions of the appendix and ovary are commonly encountered in routine practice. There are several published classification schemes for appendiceal mucinous neoplasms with resultant inconsistent use of terms and clinical doubt. While nomenclature is more settled with regards to ovarian mucinous neoplasms, the difficulty here lies with distinguishing primary from secondary mucinous tumours. This review highlights the terminology and nomenclature for appendiceal mucinous tumours, the relationship with ovarian mucinous neoplasms and pseudomyxoma peritonei, and the features that assist in separating primary from secondary ovarian mucinous tumours. [ABSTRACT FROM AUTHOR]

The Ebola virus disease outbreak in west Africa has prompted significant progress in responding to the clinical needs of patients affected by emerging infectious disease outbreaks. Among the noteworthy successes of vaccine trials, and the commendable efforts to implement clinical treatment trials during Ebola outbreaks, we should also focus on strengthening the collection and curation of epidemiological and observational data that can improve the conception and design of clinical research. [ABSTRACT FROM AUTHOR]

The article discusses the Statistical Analyses and Methods in the Published Literature (SAMPL) guidelines when submitting statistical reports of randomized controlled trials (RCT) to the "British Journal of Dermatology (BJD)." Topics covered include existing study-specific guidelines that must be used to improve reporting, the approach to use to match the research question, statistical analyses and results, and the recommended principles for reporting statistical methods.